Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary apoplexy is an acute clinical event usually caused by hemorrhage or infarction in a pituitary adenoma. We report the unusual case of hemorrhagic pituitary apoplexy in an 18 year-old male with previously undiagnosed type 2 diabetes mellitus who presented with unexplained hyperglycemia (glucose 49.2 mmol/l [887 mg/dl]) and obtundation and in whom an initial diagnosis of non-ketotic hyperglycemic coma (NKHC) was made. MRI revealed a heterogeneous mass arising from an expanded sella turcica into the suprasellar cistern. Despite well-controlled glucose levels on continuous insulin infusion, dexamethasone, and initiation of bromoergocriptine (parlodel) therapy, the patient's vision and pupillary responses deteriorated acutely. Following emergency transphenoidal surgery, the patient's vision and mental status improved. Data confirmed preoperative panhypopituitarism; serum prolactin was 396 ng/ml (microg/l). Immunostudies demonstrated tumoral labeling for prolactin, but not for ACTH, GH, TSH, LH, FSH, or P53.
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PMID:Hemorrhagic pituitary apoplexy in an 18 year-old male presenting as non-ketotic hyperglycemic coma (NKHC). 1604 31

Herein, we report the case of a 28-year old woman clinically presenting with unclear weight gain over the last years. The patient displayed facial and neck edema in combination with unobtrusive striae distensae. Endocrinological examinations led to the diagnosis of Cushing's disease. Neuroradiological examination revealed an intrasellar tumor mass of 7 mm in diameter. Subsequently, transsphenoidal tumor resection was performed. Histological and immunohistochemical investigations revealed a pituitary gland adenoma showing a biphasic tumor growth pattern with two morphologically different tumor areas producing ACTH and prolactin respectively. Co-expression of ACTH and prolactin is exceedingly rare in pituitary adenoma. To our surprise, both tumor areas exhibited features of atypia consisting in elevated MIB-1 proliferation index in the ACTH-producing portion as well as p53 expression selectively in the prolactin-producing tumor parts. To our knowledge, this is the first case of an ACTH- and prolactin-producing pituitary gland adenoma exhibiting biphasic features of atypia.
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PMID:ACTH- and prolactin-producing pituitary gland microadenoma with biphasic features of atypia and intermediate filament expression. 1664 16

A 49-yr-old woman with a large pituitary tumor leading to visual loss and galactorrhea- amenorrhea was submitted to transcranial pituitary surgery, when a clinically nonfunctioning pituitary adenoma was partially removed. Histopathology and immunohistochemistry confirmed the diagnosis of "non-secreting atypical adenoma." At that time, serum and urinary free cortisol were normal, with low T4 levels and hyperprolactinemia. The patient was discharged on thyroxine and bromocriptine and treated with conventional radiotherapy. Two years later, she presented high free urinary cortisol levels and a positive ACTH response to desmopressin testing on dexametasone 2 mg overnight. A pituitary biopsy confirmed aggressive growth as well as positive immunoreactivity for ACTH, p53, Ki-67, and c-erb-B2. The patient was then treated with radiosurgery on ketoconazole therapy. The overall clinical, laboratory, and pathological data suggest a transition from a clinically nonfunctioning to a hypersecreting ACTH-producing tumor. Putative mechanisms of tumor transformation and the possibility of a silent corticotropinoma evolving into clinical Cushing s syndrome are discussed.
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PMID:Cushing's disease arising from a clinically nonfunctioning pituitary adenoma. 1715 52

Herein, we report the case of a 73-year old male patient who presented with two recurrences of a pituitary adenoma within a period of 15 years. The first tumor resection 15 years ago revealed a non-functioning pituitary macroadenoma. 11 years later, the first recurrence of the tumor was reoperated. Throughout the early course of the disease, he suffered from secondary adrenal insufficiency and required replacement therapy with hydrocortisone. Currently, he presented with the second recurrence and clinical examination revealed signs of Cushing's disease. This was clearly confirmed by endocrinological evaluation. A retrospective analysis of all histological and immunohistochemical slides rendered an adenoma exhibiting chromophobia, ACTH-positivity and features of atypia such as elevated p53 and Ki67 expression as well as nuclear polymorphism. According to the revised WHO classification it was classified as atypical type II silent corticotroph adenoma at the time of the first and second surgery. The specimen removed during the recent surgery displayed the same histological features and was classified as corticotroph adenoma. The combination of an atypical type II adenoma and the switch in the hormone status to an endocrinologically active adenoma makes this case exceedingly rare.
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PMID:Atypical type II silent corticotrophic adenoma developing into Cushing's disease upon second recurrence. 1794 97

Excessive UVR ranks among the most harmful environmental influences on human skin. However, the direct impact of UVR on human skin appendages remains to be systematically investigated. Organ-cultured human anagen hair follicles in vitro were irradiated, and reduction of hair shaft elongation, premature catagen entry, and reduced hair matrix keratinocyte proliferation were observed upon irradiation with UVB (20/50 mJ cm(-2)). At 20 mJ cm(-2), apoptotic cell death prevailed (casp-3/p53 activation), whereas at 50 mJ cm(-2), necrotic cell death was predominant (lactate dehydrogenase increase). Mitochondrial common deletion and oxidatively damaged genomic DNA (8-OH-dG) was mainly observed at 20 mJ cm(-2). Follicular melanogenesis and ACTH immunoreactivity drastically declined, but alpha-melanocyte-stimulating hormone remained unchanged, whereas transforming growth factor-beta(2) expression shifted from the outer toward the inner root sheath. Both the number of Giemsa+ mast cells and the degree of mast-cell degranulation increased in the connective tissue sheath (CTS), and CD117 immunoreactivity of CTS cells and matrix keratinocytes was upregulated. Thus, UVR differentially modifies hair growth and cycle, promotes cell death, and induces complex regulatory events in human hair follicles in vitro. The leads from this human organ model, which is a living and human tissue interaction system under physiologically relevant in situ conditions, may encourage its use for general investigation of UV-induced effects as well as for testing possible agents for their UV-protective potency.
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PMID:Profiling the response of human hair follicles to ultraviolet radiation. 1915 39

More than 150 genes have been identified that affect skin color either directly or indirectly, and we review current understanding of physiological factors that regulate skin pigmentation. We focus on melanosome biogenesis, transport and transfer, melanogenic regulators in melanocytes, and factors derived from keratinocytes, fibroblasts, endothelial cells, hormones, inflammatory cells, and nerves. Enzymatic components of melanosomes include tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase, which depend on the functions of OA1, P, MATP, ATP7A, and BLOC-1 to synthesize eumelanins and pheomelanins. The main structural component of melanosomes is Pmel17/gp100/Silv, whose sorting involves adaptor protein 1A (AP1A), AP1B, AP2, and spectrin, as well as a chaperone-like component, MART-1. During their maturation, melanosomes move from the perinuclear area toward the plasma membrane. Microtubules, dynein, kinesin, actin filaments, Rab27a, melanophilin, myosin Va, and Slp2-a are involved in melanosome transport. Foxn1 and p53 up-regulate skin pigmentation via bFGF and POMC derivatives including alpha-MSH and ACTH, respectively. Other critical factors that affect skin pigmentation include MC1R, CREB, ASP, MITF, PAX3, SOX9/10, LEF-1/TCF, PAR-2, DKK1, SCF, HGF, GM-CSF, endothelin-1, prostaglandins, leukotrienes, thromboxanes, neurotrophins, and neuropeptides. UV radiation up-regulates most factors that increase melanogenesis. Further studies will elucidate the currently unknown functions of many other pigment genes/proteins. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.
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PMID:Physiological factors that regulate skin pigmentation. 1944 48

Nelson's syndrome (NS) is characterized by the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for the treatment of Cushing's disease. Such corticotroph macroadenomas respond poorly to currently available therapeutic options which include surgery, radiotherapy and chemotherapy. P53 protein accumulation may be detected by immunohistochemistry in pituitary corticotroph adenomas and it has been suggested that it might be causally related to tumor development. Wild type P53 protein plays an important role in the cellular response to ionizing radiation and other DNA damaging agents and is mutated in many human tumors. In this study we report an adult male patient with NS who underwent both transsphenoidal and transcranial pituitary surgeries, conventional and stereotaxic radiotherapy and brachytherapy. Despite of the efforts to control tumor mass and growth, this macroadenoma displayed relentless growth and aggressive behavior. DNA extracted from the first two surgical samples, as well as DNA from peripheral blood leukocytes disclosed normal p53 sequence. DNA extracted from tumor samples obtained at surgeries performed after pituitary irradiation carried a somatic heterozygous mutation, consisting of a deletion of four cytosines between nucleotides 12,144-12,149 in exon 4 of the p53 gene. This frameshift mutation creates a stop codon in exon 4 excluding the expression of a functional protein from the defective allele. These data demonstrate a possible association between the P53 protein loss of function induced by radiotherapy and the aggressive course of the disease in this patient.
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PMID:Possible role of a radiation-induced p53 mutation in a Nelson's syndrome patient with a fatal outcome. 1965 57

Pituitary carcinomas are a rare disease with an estimated prevalence around 0.2 % of the pituitary tumours. They are defined by the presence of intra or extra-cranial metastases but initially they can share the same features as aggressive pituitary adenomas. Indeed there are some indicators that help to differentiate adenomas and carcinomas such as histological findings and immunohistochemical characteristics. Usually in carcinomas, mitotic activity is higher, proliferative index Ki-67 is higher, p53 expression is positive and microvascular density is mostly increased. The majority of carcinomas are prolactin or ACTH-secreting tumors. Dopamine and somatostatin-receptor agonists are not as effective as for the treatment of adenomas. Carcinomas require often repeated surgery and radiotherapy fail to control the tumor. Conventional chemotherapy is poorly effective, but recent case reports with the alkylating agent temozolomide have provided better results at least in the short term. The effects of temozolomide are reversed by the enzyme MGMT and the treatment's response can be predicted by the study of MGMT's expression : tumours lacking MGMT are especially sensitive to temozolomide.
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PMID:[Pituitary carcinomas and aggressive adenomas: an overview and new therapeutic options]. 1987 63

Cushing's syndrome (CS) is characterized by pathologically elevated free glucocorticoid levels. Endogenous hypercortisolism is usually due to ACTH-secreting pituitary corticotropic adenomas and less often due to ectopic ACTH-secreting neuroendocrine neoplasms or ACTH-independent adrenal cortisol hypersecretion. CS is a serious chronic disease leading to a several-fold increase in cardiovascular morbidity and mortality. Multiple genetic alterations have been described in the setting of sporadic corticotropinoma formation. Changes in the expression profiles have been demonstrated in growth factors and their receptors, cell-cycle regulators and in various genes related to hormonal gene transcription, synthesis and secretion. Sporadic adrenal adenomas and carcinomas may demonstrate dysfunction in genes such as TP53 among others. Cushing's disease can be an inherited condition also. Multiple endocrine neoplasia type 1 (MEN1) and familial isolated pituitary adenomas (FIPA) together account for 5% of pituitary adenomas. Cushing's disease occurs infrequently in an inherited setting in both of these conditions. To date only 2 cases of Cushing's disease have been described in association with mutations in AIP. One case of Cushing's disease has been reported as part of MEN4, a rare MEN1-like syndrome due to mutation in the CDKN1B gene. Carney complex (CNC) due to PRKAR1A mutations in most cases is associated with CS, mainly as a cause of bilateral adrenal hyperplasia. The cAMP signaling pathway is affected in this setting. In recent times the involvement of genes such as PDE11A, PDE8B and others have expanded the spectrum of the genetic pathophysiology of CS.
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PMID:Genetics of Cushing's syndrome. 2082 11

The objective of this study was to describe a familial screening for AIP mutations in the context of aggressive prolactinoma in childhood. A 12-year-old boy, presented headaches and bilateral hemianopsia. He had adequate height and weight for his age (50(th) percentile), Tanner stage G1 P1. His bone age was 10 years. Prolactin was 10.560 ng/mL (3-25), FSH and LH were undetectable, IGF-1, TSH, Free T4, ACTH, and cortisol were within normal ranges. MRI showed a pituitary macroadenoma, 5.3 X 4.0 X 3.5 cm with compression of the optic chiasm, bilateral cavernous sinus invasion, encasement of carotids, and extension to clivus. Surgical debulking was performed. Resistance to cabergoline was characterized and he was submitted to two surgeries and radiotherapy. Immunohistochemical evaluation included prolactin, ACTH, GH, FSH, LH,AIP, c-erb B2, Ki-67, and p53. Genomic DNA was isolated from the index case and 48 relatives, PCR and sequencing were performed.A germline A195V mutation in AIP was identified in the index case and in five asymptomatic relatives. Germline mutations in the AIP gene may be involved in the predisposition to pituitary adenoma formation, as cause or co-factor in pathogenesis of aggressive tumors in young patients.
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PMID:Aggressive prolactinoma in a child related to germline mutation in the ARYL hydrocarbon receptor interacting protein (AIP) gene. 2134 Jan 66


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